Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.
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PMID:Pharmacological properties of new neuroleptic compounds. 0 25

GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)-ethyl] 4-(3-phenyl propenyl)-piperazine and dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the "despair test". Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.
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PMID:Comparison of the effects of three indirect dopamine agonists, GK 13, GBR 12783 and dexamphetamine on behavioural tests involving central catecholaminergic transmissions. 197 95

DL-beta-N-methylamino-alanine (DL-BMAA; 1-10 mumol i.c.v.) in mice induced a syndrome of: ataxia, ptosis, scratching, jumping, myoclonic jerks, clonic muscle spasms and tonic seizure, which was unaffected by pretreatment with D(-)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylate (D(-)-CPPene; i.p.), or by co-administration of gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS with DL-BMAA; i.c.v.). Pretreatment with 1-(aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (GYKI 52466; i.v.) decreased the incidence of clonic seizures for DL-BMAA, kainic acid and RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (RS-AMPA; i.c.v.). These results suggest an involvement of the AMPA/quisqualate subtype of excitatory amino acid receptors in acute BMAA toxicity.
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PMID:Receptor site specificity for the acute effects of beta-N-methylamino-alanine in mice. 198 Feb 47

The novel benzodioxopiperazine, S 15535 (4-(benzodioxan-5-yl)1-(indan-2- yl)piperazine), displayed high affinity for 5-HT1A binding sites (1.8 nM) whereas its affinity was 100-fold lower at other 5-HT receptor types, at alpha 1, alpha 2- and beta-adrenoceptors and at dopamine D1 and D2 receptors. In vivo, S 15535 (0.16-10 mg/kg s.c.) acted as an antagonist at postsynaptic 5-HT1A receptors in completely blocking the flat-body posture and hypothermia elicited by the 5-HT1A receptor agonist, 8-OH-DPAT. It had no effect when applied alone. At presynaptic 5-HT1A receptors, S 15535 acted as an agonist in inhibiting striatal accumulation of 5-hydroxytryptophan (0.04-0.63 mg/kg s.c.) and in spiperone reversibly reducing electrical activity of the dorsal raphe nucleus (0.004-0.031 mg/kg i.v.). At doses up to 40.0 mg/kg s.c., S 15535 neither inhibited methylphenidate-induced gnawing nor elicited ptosis suggesting a lack of antagonist properties at, respectively, dopamine D2 receptors and alpha 1-adrenoceptors. In conclusion, S 15535 is a potent 5-HT1A ligand which acts, in vivo, as a highly selective agonist and antagonist at presynaptic and postsynaptic 5-HT1A receptors, respectively.
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PMID:S 15535: a highly selective benzodioxopiperazine 5-HT1A receptor ligand which acts as an agonist and an antagonist at presynaptic and postsynaptic sites respectively. 838 59

Leaf and bark extracts of Byrsonima crassifolia displayed concentration-dependent, spasmogenic effects on rat fundus in vitro and biphasic effects on rat jejunum and ileum in vitro. Dose-related in vivo effects in intact rats using hippocratic screening were: decrease in motor activity, mild analgesia, back tonus, enophthalmos, reversible palpebral ptosis, ear blanching, Robichaud positive, catalepsy (awake) and strong hypothermia. Rat fundus in vitro was used as the bioassay to carry out an activity-directed separation. Bioactive material was concentrated in a 2% acetic acid leaf extract (HOAcE). Potency of HOAcE was increased by the presence of pargyline in the bathing solution. HOAcE was antagonized noncompetively by 1(1-naphthyl) piperazine (1-NP) and cyproheptadine and antagonized competitively by atropine (ATR). Cumulative concentration-response curves of HOAcE and serotonin (5-HT) did not show significant departure from parallelism (P > 0.1) and 5-HT potency was 6040 times that of HOAcE (95% confidence limits: 4620-7850). Solvent extraction of HOAcE split the spasmogenic activity of HOAcE into two types: (i) high-efficacy, low-potency, n-butanol-extracted, pargyline- and 1-NP-sensitive, ATR-insensitive activity, and (ii) low-efficacy, high-potency, ethyl acetate-extracted, pargyline-insensitive, ATR- and 1-NP-sensitive activity. HOAcE lacked muscarinic and nicotinic effects on rat jejunum and frog rectus abdominis. Results suggest the presence of more than one spasmogenic compound in the plant.
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PMID:Pharmacological and chemical screening of Byrsonima crassifolia, a medicinal tree from Mexico. Part I. 841 47